Approximately 600,000 people die of cardiac cell death-related diseases such as coronary heart disease (CHD), acute myocardial infarct (AMI) and congestive heart failure (CHF). Current strategies for cardiac regeneration have generated a great deal of enthusiasm and stem cell technology in particular is been widely investigated as a potential new therapy for cell death-related heart diseases. Our objectives are to differentiate a large numbers of adult stem cells into committed cardiac lineages in vitro, and to further the technology to generate functional cardiac tissue including both cardiac myocytes and coronary microvasculature in vivo. To achieve this goal, we will grow bone marrow mesenchymal stem cells (BMSCs; Sca-1 and c-kit positive, CD34 negative cells), epicardial cells and cardiac fibroblasts, separately, in collagen-based biocompatible thread-like scaffolds. These cells will be ex vivo specified into cardiac lineages using growth factors, extra cellular matrix molecules, and intercellular interactions provided by 3-dimensional arrangements of the scaffolds. The most effective 3-D cellular construct will be transplanted into the myocardial infarcted area of a rat heart to test its survival, further differentiation and establishment of electromechanical connections to the neighboring host cardiac tissue. Our long-term goal is to develop autologous stem cell implants for MI patients.